Functional mitral regurgitation (MR) plays a pivotal role in the pathophysiology of the congestive heart failure (CHF), a major cause of cardiac morbidity and mortality. Surgical therapy for functional MR has been limited in patients with severe CHF by relatively high operative mortality rates due to the effects of cardiopulmonary bypass and sternotomy. Therefore, there is a need for a minimally invasive method to treat MR to reduce patient risk. The purpose of this proposed program is to develop a new procedure for MR treatment: mitral annular remodeling resulting from a non-absorbable substance injection into the posterior mitral annulus. This procedure may enable the septal-lateral dimension to be efficiently reduced thus reducing MR without employing cardiopulmonary bypass or implanting a device into the coronary sinus. If this mitral annular remodeling proves to be efficacious in reducing functional MR, further development of a new device that will allow for percutaneously injection of the substance through the coronary sinus will be undertaken in the future. Therefore, as a first step in this process, we propose to evaluate the effects of mitral annular remodeling resulting from a nonabsorbable substance injection using an epicardial approach. To achieve this goal, the Specific Aims of this proposed program are: (1) to assess the feasibility of a precise injection of a nonabsorbable substance into the posterior mitral annulus on a beating heart in healthy canines, (2) to evaluate acute effects of mitral annular remodeling on the geometry of the mitral apparatus and the degree of MR in a canine tachycardia-induced MR model, and (3) to evaluate long-term effects of mitral annular remodeling on MR, tissue reaction, coronary circulation, and LV function by comparison with a tachycardia-induced MR Control group. Successful completion of this research program will provide us with preliminary data that will support our future program in which the development of a new percutaneously delivered device will allow for injection of the substance through the coronary sinus. Therefore, this proposed research program is an important first step in this novel procedure's development as one potential therapeutic option for high-risk CHF patients with functional MR.